The metabolic and microcirculatory impact of orthotopic liver transplantation on the obese Zucker rat.

Background: The purpose of this study was to investigate the metabolic alterations in the recipient and microcirculatory changes to the graft in the first 3 months after orthotopic liver transplantation (OLT) of nonsteatotic liver grafts from lean rats into obese Zucker rats.

Methods: Body weight and plasma lipids were measured for 3 months post-OLT. Graft perfusion (hepatic microcirculatory perfusion [HMP]) and vascular structure were measured in vivo at 3 months. Liver biopsy specimens were obtained throughout for morphologic analysis. Sham-operation obese and lean Zucker rats acted as controls.

Results: Plasma cholesterol levels were elevated from 2 months after OLT, whereas plasma triglyceride levels were reduced (P<0.05). Plasma high-density lipoprotein cholesterol concentrations increased from the first month after OLT (P<0.05). HMP in OLT animals (137+/-3 perfusion units [PU]) (P<0.05) was intermediate between lean (221+/-11 PU) and obese controls (113+/-5 PU). Hepatic cord width in the OLT group was similar to that in lean controls. Mean liver-to-body weight ratios in OLT animals (4.12%+/-0.39%) were significantly higher than in lean controls (3.25%+/-0.1%). The number of viable hepatocytes per high-power field in the OLT animals was lower than in the lean animals but higher than in obese controls (P<0.05). The transplanted livers showed moderate to marked microvesicular fatty change (MIFC) and glycogen deposition at 3 months after OLT.

Conclusions: Transplantation of a nonsteatotic liver into an obese Zucker rat initially has a positive effect on lipid metabolism. However, 3 months after OLT, the donor liver became steatotic with MIFC changes and reduced perfusion. The authors' results emphasize the importance of the recipient's metabolic status in the maintenance of liver graft function after OLT.